•We show how many materials aging issues exhibit hallmarks of mesoscale science.•Combining theory, multiscale simulation, and experiments yields new insights.•Colloidal flow and radiation void swelling are given as illustrative examples.•These approaches can apply broadly to solve longstanding issues in materials aging. The complexity of materials aging may be seen as a result of the interplay between several activation processes operating on multiple spatial and temporal scales. Though the disciplines involved may seem disparate at first, material aging fundamentally could be linked by the same set of underlying activations and responses of the system. We examine how recent studies of shear-induced deformation and rheological flow initiated in the soft-matter community can be leveraged to probe the mechanisms of radiation damage in nuclear materials. Bridging these two traditionally separate areas of research demonstrates the emerging notions of mesoscale science as a research frontier concerned with linking macroscale behavior to microscale processes in driven systems. We suggest the combining of microstructure-sensitive measurements with fundamental theories and mechanism-specific simulations is essential to addressing metastable materials responses of strongly activated states.